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Effect of Sorafenib on ccRCC Uptake of Radiolabeled Bevacizumab or cG250

NCT ID: NCT00602862

Last Updated: 2013-12-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-07-31

Study Completion Date

2012-06-30

Brief Summary

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Sorafenib is a tyrosine kinase inhibitor that is registered for the treatment of metastasized clear cell Renal Cell Carcinoma (ccRCC). It inhibits signal transduction of the Vascular Endothelial Growth Factor Receptor (VEGFR) and the Platelet Derived Growth Factor Receptor (PDGFR). In the tumorigenesis of ccRCC, VEGF and PDGF are upregulated due to the defective Von-Hippel-Lindau (VHL) gene. CcRCC has a high Interstitial Fluid Pressure (IFP) and Tumor Microvascular Density (TMD), hampering the delivery of chemotherapeutics and monoclonal antibodies (mAbs). It was hypothesized that antiangiogenic compounds decrease tumor IFP and TMD, thus normalizing tumor vasculature, before diminishing tumor vasculature. Bevacizumab is an anti-VEGF mAb which depletes soluble VEGF from plasma, depriving VEGFR of its ligand. Chimeric monoclonal antibody cG250 recognizes carbonic anhydrase IX (CAIX), an antigen that is abundantly expressed in Renal Cell Carcinoma (RCC) and has limited expression in normal tissue. The aim of this study was to investigate the effect of Sorafenib on ccRCC physiology, by determining tumor uptake of 111In labeled cG250 or 111In labeled Bevacizumab.

Detailed Description

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Conditions

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Clear Cell Renal Cell Carcinoma

Keywords

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Angiogenesis inhibitors

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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1

10 Patients planned to undergo (partial) nephrectomy or metastasectomy receive an iv injection of 100 MBq/1mg 111In-Bevacizumab. Patients are then treated with Sorafenib 200 mg 2dd2 po for 4 weeks. In the last week of treatment, the same injection is given to determine tumor accumulation of the radiolabeled mAb after Sorafenib treatment. Whole-body scintigraphic images are recorded 1 week after both injections to calculate tumor uptake. After Sorafenib treatment, patients will undergo surgery.

Group Type EXPERIMENTAL

Sorafenib

Intervention Type DRUG

Sorafenib 200 mg 2dd2 po for 4 weeks before surgery

111Indium-bevacizumab

Intervention Type DRUG

100 MBq / 1 mg 111Indium/bevacizumab iv

2

10 Patients planned to undergo (partial) nephrectomy or metastasectomy receive an iv injection of 100 MBq/10mg 111In-cG250. Patients are then treated with Sorafenib 200 mg 2dd2 po for 4 weeks. In the last week of treatment, the same injection is given to determine tumor accumulation of the radiolabeled mAb after Sorafenib treatment. Whole-body scintigraphic images are recorded 1 week after both injections to calculate tumor uptake. After Sorafenib treatment, patients will undergo surgery.

Group Type EXPERIMENTAL

Sorafenib

Intervention Type DRUG

Sorafenib 200 mg 2dd2 po for 4 weeks before surgery

111Indium-cG250

Intervention Type DRUG

100 MBq / 10 mg 111Indium-cG250 iv

3

5 Patients planned to undergo (partial) nephrectomy or metastasectomy receive an iv injection of 100 MBq/1mg 111In-Bevacizumab. Whole-body scintigraphic images are recorded 1 week after the injection to calculate tumor uptake. Hereafter, patients will undergo surgery.

Group Type ACTIVE_COMPARATOR

111Indium-bevacizumab

Intervention Type DRUG

100 MBq / 1 mg 111Indium/bevacizumab iv

Interventions

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Sorafenib

Sorafenib 200 mg 2dd2 po for 4 weeks before surgery

Intervention Type DRUG

111Indium-bevacizumab

100 MBq / 1 mg 111Indium/bevacizumab iv

Intervention Type DRUG

111Indium-cG250

100 MBq / 10 mg 111Indium-cG250 iv

Intervention Type DRUG

Other Intervention Names

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Bevacizumab Avastin Nexavar cG250 Rencarex avastin indium rencarex indium

Eligibility Criteria

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Inclusion Criteria

* Renal cell carcinoma patients planned for surgery (nephrectomy/metastasectomy)
* Karnofsky \> 70 %
* Laboratory values within 14 days prior to start:

* White blood cells (WBC) \> 3.5 x 109/L
* Platelets \> 100 x 109/L
* Hemoglobin \> 6 mmol/L
* Total bilirubin \< 1.5 upper limit of normal (ULN)
* ASAT, ALAT \< 2.5 x ULN (\<5 x in case of liver metastases)
* Lactate dehydrogenase (LDH) \> 1.5. ULN
* Serum creatinine \< 2 x ULN
* Amylase and Lipase \< 1.5 ULN
* Negative pregnancy test in premenopausal women
* Age over 18 years
* Signed informed consent
* Life expectancy \> 24 weeks
* PT/APTT/ INR \< 1.5 ULN
* No current use of coumarin derivatives

Exclusion Criteria

* Known subtype other than clear cell RCC
* Pre-exposure to murine/chimeric antibody therapy
* Known brain metastases
* Untreated hypercalcemia
* Uncontrolled hypertension
* Concurrent therapeutic anticoagulation
* Chemotherapy, immunotherapy or radiation therapy within 4 weeks prior to start of study. Palliative limited field external radiation for fracture prevention is allowed
* Cardiac arrhythmias requiring antiarrhythmics (beta-blockers, digoxin), symptomatic coronary artery disease and congestive heart failure New York Heart Association III or IV.
* Previous malignancy \< 2 years prior to the study (except for cervical carcinoma in situ, basal cell carcinoma, or superficial bladder tumours (Ta, Tis, T1)
* Any medical condition present that in the opinion of the investigator will affect patients' clinical status. No other concurrent malignancy except nonmetastatic nonmelanoma skin cancer or carcinoma in situ of the cervix.
* Active clinically serious bacterial or fungal infections (\< grade 2 NCI-CTC version 3)
* Known history of Human Immunodeficiency virus (HIV) infection or chronic hepatitis B/C.
* Prior use of Raf-kinase inhibitors, MEK and Farnesyl transferase inhibitors
* Prior use of Bevacizumab and all other drugs that target VEGF/ VEGF-receptors
* Use of antiepileptic drugs
* Pregnancy and lactation
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Dutch Cancer Society

OTHER

Sponsor Role collaborator

Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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WJG Oyen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Nuclear Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

PFA Mulders, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Urology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Locations

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Radboud University Nijmegen Medical Center

Nijmegen, Gelderland, Netherlands

Site Status

Countries

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Netherlands

References

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Desar IM, Stillebroer AB, Oosterwijk E, Leenders WP, van Herpen CM, van der Graaf WT, Boerman OC, Mulders PF, Oyen WJ. 111In-bevacizumab imaging of renal cell cancer and evaluation of neoadjuvant treatment with the vascular endothelial growth factor receptor inhibitor sorafenib. J Nucl Med. 2010 Nov;51(11):1707-15. doi: 10.2967/jnumed.110.078030. Epub 2010 Oct 18.

Reference Type DERIVED
PMID: 20956472 (View on PubMed)

Other Identifiers

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Sorafenib-mAbs

Identifier Type: -

Identifier Source: org_study_id